Inhibitory effect of Sargassum latifolium extract on hypoxia pathway in colon cancer cells

  • Amira M. Gamal- Eldeen Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taif ‎University, P.O. Box 11099, Taif 21944, Saudi Arabia; High Altitude Research Center, Prince Sultan Medical Complex, Al-Hawiyah, Taif ‎University, Taif, Saudi Arabia
  • Bassem M. Raafat Radiological Sciences Department, College of Applied Medical Sciences, Taif University, ‎P.O. Box 11099, Taif 21944, Saudi Arabia
  • Sherien M. ‎El- Daly Medical Biochemistry Department, Medical Research Division, National Research Centre, ‎‎33 El Buhouth St. Dokki, Cairo, 12622, Egypt‎; Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, ‎National Research Centre, 33 El Buhouth St. Dokki, Cairo, 12622, Egypt
  • Cinderella A. Fahmy Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, ‎National Research Centre, 33 El Buhouth St. Dokki, Cairo, 12622, Egypt; Biochemistry Department, Medical Research Division, National Research Centre, ‎‎33 El Buhouth St. Dokki, Cairo, 12622, Egypt‎
  • Mazen M Almehmadi Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taif ‎University, P.O. Box 11099, Taif 21944, Saudi Arabia
  • Fayez Althobaiti High Altitude Research Center, Prince Sultan Medical Complex, Al-Hawiyah, Taif ‎University, Taif, Saudi Arabia; Biotechnology Department, Faculty of Science, Taif University, P.O. Box 11099, Taif ‎‎21944, ‎Saudi Arabia

Abstract

Sargassum latifolium, ‎(Turner) C. Agarth, 1820, is an edible brown alga that was collected from red seashores in Egypt. Colon cancer is a lethal disease world-wide. Hypoxia is a key player in progressive colon tumor growth and stemness. This work was planned to extract water-soluble polysaccharide from S. latifolium, to separate its fractions (SL1, SL2, SL3, and SL4) and hence to investigate their anti-hypoxia characteristics in colon cancer HCT-116 cells. Algal fractions cytotoxicity was assayed by MTT; DNA staining was used to analyze apoptosis and necrosis; total hypoxia status was assessed by pimonidazole, HIF-1α and HIF-1β were estimated by ELISA, and hsa-miRNA-21-5p and hsa-miRNA-210-3p were analyzed by qPCR. The results indicated that SL1 and SL4 are cytotoxic agents against HCT-116 cells through enhancing apoptosis. SL1and SL4 were potent inhibitor of total cell hypoxia (p < 0.001). Both fractions significantly suppressed the expression of miR-21 (p < 0.01) and miR-210 (p < 0.001), and the concentration of HIF-1α protein (p < 0.01 and p < 0.001, respectively), while only SL1 inhibited HIF-1β protein concentration (p < 0.05). Taken together S. latifolium polysaccharide extract fractions SL1 and SL4 exhibited anti-hypoxic property in HCT-116 cells through mechanistic role in the expression of hypoxia regulators miRNA-21 and miRNA-210, and accordingly in HIF-1α and HIF-1β biosynthesis‎.

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